During the next 2 months she operated with a patrol and escort group out of NS Argentia, Newfoundland, and on 5 August 1943 departed for England with troop ship RMS Queen Mary.

Isherwood arrived Scapa Flow 19 August to carry out combined operations with the British Home Fleet, including a search toward Spitzbergen for German battleship Tirpitz.

Isherwood remained in the assault area during the giant four-part Battle for Leyte Gulf 23–26 October, in which the Japanese surface fleet was all but annihilated.

During the last days of the month, specifically 29 and 30 January, the ship returned to Luzon to support the unopposed landings at San Antonio and Subic Bay, as ground units moved on Manila.

Troops from the main task force stormed ashore 1 April in the biggest amphibious operation of the Pacific war, and 2 days later Isherwood moved to a position off the beaches for fire support missions.

The days that followed found Isherwood in numerous heavy air raids, as the Japanese made a desperate attempt to drive off the invasion fleet with suicide planes.

After taking part in the Navy Day Presidential Review, the ship steamed to Charleston, where she decommissioned 1 February 1946 and was placed in the Atlantic Reserve Fleet.

This was the first US Navy visit to an Australian port, and the country welcomed the ships by opening a national park in Sidney, commemorating the Battle of Coral Sea.

During the 1958, she steamed off Taiwan during the tense Quemoy-Matsu crisis, when American forces afloat helped prevent a flareup between Nationalist and Communist China.

The ship returned to her home port of San Diego on 7 December 1958, and spent the first 6 months of 1959 on maneuvers and training exercises after refitting in Mare Island (Vallejo) Navy Yard.

During the next months she operated with carrier Lexington (CV-16) in the South China Sea, helping to limit the fighting in Laos and lending strength to United Nations efforts to find a solution.